These studies focus on two topics: ovarian cancer and the Wnt pathway in human cancers. Ovarian cancer is the fifth most common cancer and the fourth leading cause of cancer death among women in the United States. Because of a lack of powerful screening and diagnostic tests, early detection has been difficult. Moreover, the molecular mechanism involved in the initiation and progression of ovarian cancer remain largely unknown. We are using SAGE and other state-of-the-art molecular techniques to identify tumor markers and gain a greater understanding of the molecular pathways involved in ovarian tumorigenesis. In addition, we are interested in a region on the X chromosome, which is frequently lost in high grade ovarian cancers, suggesting the presence of a tumor suppressor gene involved late in ovarian tumor development. We are in the process of characterizing candidates for this tumor suppressor gene. The Wnt pathway, which was originally defined as a crucial pathway for body patterning during fruit fly development, has recently been involved in human cancer. APC, a gene mutated in 80% of all colon cancers, is involved in the downregulation of the Wnt pathway. Moreover, colon tumors containing wild-type APC, frequently contain activating mutations in other members of the pathway emphasizing its importance for colon cancer progression. We are investigating other human tumors, especially ovarian cancer, for the presence of alterations in the WNT pathway. In addition, we are interested in identifying downstream targets of the pathway as well as upstream regulatory components.